We have previously shown that mutation of phosphorylation sites Ser 315 and Ser 392 to alanine did not alter the ability of p53 to inhibit the growth of tumor cell line SW480. It was proposed that p53 may serve as a transcriptional enhancer. To obtain more insight into the molecular events, we utilized a transfection assay which monitors the expression of a reporter gene, chloramphenicol acetyl transferase (CAT), to study the effects of mutated phosphorylation sites on p53 function. We found that removal of phosphorylation sites did not affect the ability of p53 to stimulate production of the CAT enzyme. Thus, it appears that phosphorylation of Ser 315 or Ser 392 does not directly modulate the functional activity of p53. Others have reported that accumulation of p53 protein accompanies the cellular response to DNA damage. It is possible that phosphorylation regulated by external or internal stimuli may affect p53 function indirectly by stabilizing the protein and allowing for its accumulation. We are in the process of exploring the possible effects of phosphorylation on p53 stability using in vitro and in vivo methods. In addition, we are also in the process of examining the effects of dietary compounds which may modulate p53 accumulation.